The trans-sulfuration pathway is a biochemical mechanism that links methionine metabolism to the biosynthesis of cellular redox-controlling molecules, like cysteine, glutathione, and taurine. While there is some knowledge about the metabolic intermediates and enzymes that participate in trans-sulfuration, little is known about the physiological importance of this mechanism. Deficiencies within the trans-sulfuration pathway induces (i) the generation of reactive species of oxygen (ROS) and halogens (RHS), (ii) homocyst(e)ine accumulation, and (iii) the synthesis of proinflammatory molecules by macrophages, and contribute to humans pathologies like atherosclerosis and tumor development. In this review we outline the role of this biochemical pathway in tumor development and analyze current findings on the role of trans-sulfuration in mammalian physiology. The potential relationship between chronic inflammation, and tumor and atherosclerotic development are discussed.